EFFECTS OF HALOTHANE ON THE NICOTINIC ACETYLCHOLINE-RECEPTOR FROM TORPEDO-CALIFORNICA

To determine whether the binding of anesthetics to key membrane recept ors is a plausible mode of action, we modeled the effect of the genera l anesthetic halothane in the nicotinic acetylcholine receptor membran e system isolated from Torpedo californica. Our results demonstrated t hat halothane inhibits the binding of [H-3]phencyclidine ([H-3]PCP) to the acetylcholine receptor. The inhibition was reversible, concentrat ion dependent, and had an equilibrium dissociation constant (K-d) of 2 .2% atm halothane at 25 degrees. Double-reciprocal plots of the haloth ane effects at Various phencyclidine (PCP) concentrations imply that, under equilibrium conditions, halothane inhibits [H-3]PCP binding comp etitively. In contrast, results from kinetic studies showed that the r ate of PCP dissociation is highly sensitive to halothane with EC(50) = 0.8% atm halothane in nitrogen. Several possible interpretations are discussed; however, the basic observation was that the kinetics of [H- 3]PCP binding to the nicotinic acetylcholine receptor was affected by halothane at low concentrations in this model system.